Central and peripheral glucocorticoid receptor function in abdominal obesity

Area of Science:

• Endocrinology
• Metabolic Research
• Molecular Biology

Background:

• Abdominal obesity is associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.
• Central glucocorticoid receptors (GR) play a role in HPA axis feedback regulation.
• Trinucleotide repeats in steroid hormone receptor genes may influence receptor density and function.

Purpose of the Study:

• To compare the functions of central and peripheral GR in men with and without abdominal obesity.
• To investigate the potential role of trinucleotide repeat expansion in the GR gene in abdominal obesity.
• To elucidate the relationship between HPA axis function and peripheral GR activity in abdominal obesity.

Main Methods:

• Dose-response dexamethasone suppression tests were used to assess central GR function by measuring serum cortisol levels.
• Lipoprotein lipase (LPL) activity in abdominal adipose tissue biopsies was measured to assess peripheral GR function.
• Genomic DNA sequencing was performed to analyze trinucleotide repeats in the GR gene.

Main Results:

• Men with abdominal obesity exhibited reduced cortisol suppression by dexamethasone, indicating impaired central GR function.
• Lipoprotein lipase (LPL) activity was lower in abdominal obese men, but their adipose tissue sensitivity to cortisol was not different from controls.
• No expansion of trinucleotide repeats in the GR gene was observed in either group.

Conclusions:

• Central and peripheral GR exhibit distinct functional alterations in the context of abdominal obesity.
• The findings suggest a deranged feedback regulation of the HPA axis in abdominal obesity, primarily involving central GR dysfunction.
• Trinucleotide repeat expansion in the GR gene does not appear to be a contributing factor to abdominal obesity in this cohort.